Completion of Gene-to-Lead phase for first discovery project
targeting METTL3/METTL14 complex

NEW YORK & LEIDEN, Netherlands–(BUSINESS WIRE)–Gotham
Therapeutics, a biotechnology company developing a novel drug class
targeting RNA-modifying proteins, and ZoBio,
the leading contract research organization in integrated fragment-based
drug discovery, today announced significant progress made as part of
their collaboration to identify therapeutic lead candidates for Gotham’s
initial portfolio of epitranscriptomic targets. In the first project
pursued within the collaboration, the initial phase for Gotham’s drug
discovery project targeting the METTL3/METTL14 complex has been
completed and a portfolio of small-molecule candidates will be further
evaluated.

“In a sector that is still in its infancy, we have made tangible
progress with our partner ZoBio to develop small molecule leads against
a portfolio of epitranscriptomic targets just 14 months after initiation
of the project,” commented Dr. Lee Babiss, Chief Executive Officer of
Gotham Therapeutics. “Today’s news is also a validation of the
semi-virtual model we use and the productivity of our network with
best-in-class CROs.”

“With METTL3/METTL14 being among the more obvious approaches in
epitranscriptomics, the quality of the chemical matter pursued is going
to be a key differentiating factor,” added Dr. Gerhard Müller, Chief
Scientific Officer of Gotham Therapeutics. “Together with ZoBio, we have
not just successfully identified the initial candidates for Gotham’s
first pipeline program but also established a robust process from gene
to lead as a platform for additional projects to come.”

“The unique combination of our expertise and technologies allows us to
initiate programs to pursue inhibitors of pharmacological targets that
have been previously out of reach,” added Dr. Gregg Siegal, Chief
Executive Officer of ZoBio. “We are pleased to have been able to use our
intellectual and technological resources to enable Gotham’s drug
discovery program and to further the newly developed field of
epitranscriptomics. We look forward to continued work with the Gotham
team and to continued advancements in this new field of biology.”

In January 2018, Gotham and ZoBio initiated a collaboration to develop
small-molecule inhibitors of the “writer” protein complex
METTL3/METTL14, a SAM-dependent methyltransferase that modifies mRNA
encoded adenosine in the messenger RNA to m⁶A and thereby
regulates protein expression. The collaboration aims to use ZoBio’s
unique capabilities in biophysics-based drug discovery and structural
biology to attack this novel target. Through extensive protein
engineering, multiple forms of the complex have been generated that
enable all of the planned studies. Using Surface Plasmon Resonance to
screen ZoBio’s diverse fragment library, the collaboration has resulted
in the discovery and validation of multiple, drug-like substances that
selectively modulate the function of the METTL3/METTL14 complex and have
the potential to be optimized towards pre-clinical candidates. ZoBio’s
unique expertise in both Nuclear Magnetic Resonance spectroscopy and
protein crystallography has enabled the deep understanding of the mode
of action of these chemotypes at atomic resolution. With their combined
arsenal of capabilities and expertise, Gotham and ZoBio are well
positioned to generate in vitro and in vivo active
inhibitors that will further Gotham’s programs and the field of
epitranscriptomics.

About Gotham Therapeutics:
Gotham Therapeutics has assembled
an exceptional team and network to establish a novel drug class
targeting RNA-modifying proteins. By changing the activity of proteins
that modify messenger RNA, we aim to develop new treatment options for
patients suffering from cancers, auto-immune and neurodegenerative
diseases. We are applying a 360-degree approach to small molecule drug
design to build a pipeline based on the promise of this rapidly emerging
biopharmaceutical field. For more information, please visit: www.gothamtx.com

About ZoBio:
ZoBio offers proprietary, orthogonal technology
and more than 15 years of experience to enable its integrated
fragment-based drug discovery engine for a wide range of pharmaceutical
targets. The engine is based on a platform of high throughput protein
engineering, highly diverse fragment libraries, proprietary biophysical
screening technologies and complementary structural biology approaches
designed to provide data in the broadest possible target space. We
synthesize this information to generate actionable medicinal chemistry
hypotheses to bridge the divide between fragment and lead. For more
information, please visit: www.zobio.com

Contacts

Gotham Therapeutics:
Dr. Birgit Zech
Chief Operating
Officer
+49 179 5340884
bzech@gothamtx.com

Media Contact:
Mario Brkulj and Amanda Houlihan
MacDougall
+49
175 5711562 or +1 781-235-3060
gotham@macbiocom.com

ZoBio:
Dr. Gregg Siegal
Chief Executive Officer
+31
71 204 05 80
gsiegal@zobio.com